Atropiniques et développement infantile : étude EFEMERIS

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SUPPLEMENTARY
Figure S1. Selection of the study population (2004-2010).
EFEMERIS cohort (2004-2010)
N= 55,035 “mother-outcome” pairs
Excluded
- Not at least one health certificate at 9
months or 24 months: n= 11,295
Population to study
N= 43,740 “mother-child” pairs

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Table S1. List of drugs with atropinic properties used by study participants.
High potency atropinics
Low potency atropinics
Acepromazine
Alimemazine
Aceprometazine
Azelastine
Amitriptyline
Baclofene
Brompheniramine
Bromocriptine
Chlorphenamine
Carbamazepine
Chlorpromazine
Cetirizine
Clomipramine
Cimetidine
Cyamemazine
Citalopram
Dexchlorpheniramine
Clonazepam
Doxepine
Codeine
Flavoxate
Dextropropoxyphene
Fluphenazine
Diazepam
Hydroxyzine
Domperidone
Imipramine
Dosulepine
Ipratropium bromure
Entacapone
Levomepromazine
Fentanyl
Maprotiline
Fexofenadine
Meclozine
Flunarizine
Mequitazine
Fluoxetine
Metopimazine
Flupentixol
Oxomemazine
Fluvoxamine
Oxybutynine
Haloperidol
Pipotiazine
Indoramine
Promethazine
Lithium
Trihexyphenidyl
Loperamide
Trimipramine
Loratadine
Tropatepine
Loxapine
Methadone
Methocarbamol
Mirtazapine
Mizolastine
Morphine
Olanzapine
Oxcarbazepine
Oxycodone
Paroxetine
Pizotifene
Quinidine
Ranitidine
Risperidone
Theophylline
Tramadol

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Table S2. Primary analyses. Risk of abnormalities of psychological development at 9 and 24 months
following in utero atropinic burden exposure in 2 groups (complete case).
Outcomes
Odds Ratios (95% CI)
Crude
Adjusted*
At 9 months
Unable to repeat a syllable
1.07 (0.95-1.20)
1.11 (0.96-1.29)
No reaction to own name
1.09 (0.88-1.35)
1.01 (0.78-1.32)
Unable to point the finger
0.98 (0.92-1.04)
0.99 (0.92-1.06)
Unable to play ‘peek-a-boo’
1.05 (0.94-1.18)
1.01 (0.88-1.15)
At 24 months
Unable to understanding a simple instruction
1.50 (1.08-2.10)
1.41 (0.90-2.23)
Unable to name a picture
1.19 (1.04-1.37)
1.32 (1.11-1.57)
Unable to associate two words
1.07 (0.95-1.21)
1.09 (0.94-1.26)
* Adjusted on maternal age at birth, unemployed, maternal smoking during pregnancy, diabetes, long-term adverse health condition, number
of different substances prescribed during pregnancy, sex of the child, prematurity, multiple pregnancy, APGAR at 5 min ≤ 7, major
congenital anomaly, pathology during the first week of life, and infant breastfed during the first week.

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Table S3. Secondary analyses. Risk of abnormalities of psychological development at 9 and 24 months
following in utero atropinic burden exposure in 4 groups (complete case).
Outcomes
Odds ratios (95% CI)
Unadjusted
Adjusted
At 9 months
Unable to repeat a syllable
score = 0
ref= 1
ref= 1
score [1-8]
1.04 (0.93-1.18)
1.09 (0.93-1.27)
score [9-17]
1.60 (1.02-2.52)
1.89 (1.10-3.25)
score ≥ 18
2.43 (1.09-5.43)
1.99 (0.66-6.03)
No reaction to own name
score = 0
ref= 1
ref= 1
score [1-8]
1.07 (0.87-1.33)
1.00 (0.76-1.31)
score [9-17]
1.44 (0.61-3.37)
1.59 (0.62-4.09)
score ≥ 18
3.04 (0.85-10.80)
1.88 (0.35-9.99)
Unable to point the finger
score = 0
ref= 1
ref= 1
score [1-8]
0.98 (0.92-1.04)
0.98 (0.92-1.06)
score [9-17]
1.09 (0.83-1.42)
1.17 (0.85-1.61)
score ≥ 18
0.65 (0.31-1.36)
0.56 (0.23-1.41)
Unable to play ‘peek-a-boo’
score = 0
ref= 1
ref= 1
score [1-8]
1.05 (0.94-1.18)
1.01 (0.88-1.15)
score [9-17]
1.17 (0.72-1.90)
1.15 (0.63-2.11)
score ≥ 18
1.25 (0.42-3.74)
1.19 (0.32-4.36)
At 24 months
Unable to understand a simple instruction
score = 0
ref= 1
ref= 1
score [1-8]
1.54 (1.10-2.15)
1.43 (0.91-2.26)
score [9-17]
1.22 (0.24-6.18)
1.94 (0.38-9.85)
score ≥ 18
1.96 (0.12-32.63)
3·89 (0·23-66·58)
Unable to name an image
score = 0
ref= 1
ref= 1
score [1-8]
1.16 (1.01-1.34)
1.29 (1.08-1.54)
score [9-17]
2.32 (1.44-3.75)
2.39 (1.33-4.29)
score ≥ 18
1.47 (0.41-5.27)
2.70 (0.73-10.04)
Unable to associate two words
score = 0
ref= 1
ref= 1
score [1-8]
1.06 (0.94-1.20)
1.09 (0.94-1.26)
score [9-17]
0.91 (0.50-1.66)
0.90 (0.43-1.89)
score ≥ 18
4.03 (1.79-9.08)
2.91 (0.90-9.36)
* Adjusted on maternal age at birth, unemployed, maternal smoking during pregnancy, diabetes, long-term adverse health condition, number
of different substances prescribed during pregnancy, sex of the child, prematurity, multiple pregnancy, APGAR at 5 min ≤ 7, major
congenital anomaly, pathology during the first week of life, and infant breastfed during the first week.

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Table S4. Sensitivity analyses. Risk of abnormalities of psychological development at 9 and 24 months
following in utero atropinic burden exposure in 2 groups after exclusion of women exposed to
psychotropics (imputated dataset).
Outcomes
Score=0
Score ≥ 1
Odds Ratios (95% CI)
No with outcome /total no (%)
Crude
Adjusted*
At 9 months
Unable to repeat a syllable
772/25819 (3.0)
361/11638 (3.1)
1.04 (0.92-1.18)
1.04 (0.91-1.18)
No reaction to own name
228/25862 (0.9)
110/11662 (0.9)
1.07 (0.85-1.35)
1.06 (0.84-1.34)
Unable to point the finger
3940/17345 (22.7)
1728/7722 (22.4)
0.98 (0.92-1.05)
0.98 (0.92-1.05)
Unable to play ‘peek-a-boo’
893/17412 (5.1)
407/7735(5.3)
1.03 (0.91-1.16)
1.02 (0.90-1.15)
At 24 months
Unable to understand a simple instruction
71/19996 (0.4)
51/9123 (0.6)
1.58 (1.10-2.26)
1.71 (1.16-2.50)
Unable to name an image
504/19965 (2.5)
275/9105 (3.0)
1.20 (1.04-1.40)
1.20 (1.03-1.39)
Unable to associate two words
771/13535 (5.7)
366/6114 (6.0)
1.06 (0.93-1.20)
1.06 (0.93-1.20)
* Adjusted on maternal age at birth, unemployed, maternal smoking during pregnancy, diabetes, long-term adverse health condition, number
of different substances prescribed during pregnancy, sex of the child, prematurity, multiple pregnancy, APGAR at 5 min ≤ 7, major
congenital anomaly, pathology during the first week of life, and infant breastfed during the first week.